Rab11a drives adhesion molecules to the surface of endometrial epithelial cells.

STUDY QUESTION: Is Rab11a GTPase, a regulator of intracellular trafficking, of significance in endometrial functions? SUMMARY ANSWER: Rab11a is an important component of the cascades involved in equipping the endometrial epithelium (EE) with 'adhesiveness' and 'cohesiveness'. WHAT IS KNOWN ALREADY: Cell adhesion molecules (CAMs) have been investigated extensively for modulation in their endometrial expression during the peri-implantation phase. However, the mechanisms by which CAMs are transported to the EE surface have not received the same attention. Rab11a facilitates transport of specific proteins to the plasma membrane in endothelial cells, fibroblasts, embryonic ectodermal cells, etc. However, its role in the transport of CAMs in EE remains unexplored. STUDY DESIGN, SIZE, DURATION: In-vitro investigations were directed towards deciphering the role of Rab11a in trafficking of CAMs (integrins and E-cadherin) to the cell surface of Ishikawa, an EE cell line. Towards this, Rab11a stable knockdown (Rab-kd) and control clones of Ishikawa were generated. JAr (human trophoblastic cell line) cells were used to form multicellular spheroids. Pre-receptive (n = 6) and receptive (n = 6) phase endometrial tissues from women with proven fertility and receptive phase (n = 6) endometrial tissues from women with unexplained infertility were used. PARTICIPANTS/MATERIALS, SETTING, METHODS: Rab-kd and control clones were used for in-vitro assays. Live cells were used for biotinylation, JAr spheroid assays, flow cytometry, trans-epithelial electrical resistance assays and wound-healing assays. Lysosome and Golgi membranes were isolated by ultracentrifugation. Confocal microscopy, immunoblotting, qRT-PCR and immunohistochemistry were employed for assessing the expression of Rab11a, integrins and E-cadherin. MAIN RESULTS AND THE ROLE OF CHANCE: shRNA-mediated attenuation of Rab11a expression led to a significant (P < 0.01) decline in the surface localization of αVß3 integrin. Cell surface protein extracts of Rab-kd clones showed a significant (P < 0.05) reduction in the levels of αV integrin. Further, a significant (P < 0.01) decrease was observed in the percent JAr spheroids attached to Rab-kd clones, compared to control clones. Rab-kd clones also showed a significant (P < 0.001) decline in the total levels of E-cadherin. This was caused neither by reduced transcription nor by increased lysosomal degradation. The role of Rab11a in maintaining the epithelial nature of the cells was evident by a significant increase in the migratory potential, presence of stress-fibres and a decrease in the trans-epithelial resistance in Rab-kd monolayers. Further, the levels of endometrial Rab11a and E-cadherin in the receptive phase were found to be significantly (P < 0.05) lower in women with unexplained infertility compared to that in fertile women. Taken together, these observations hint at a key role of Rab11a in the trafficking of αVß3 integrin and maintenance of E-cadherin levels at the surface of EE cells. LARGE-SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: The in-vitro setting of the study is a limitation. Further immunohistochemical localizations of Rab11a and CAMs were conducted on a limited number of human endometrial samples. WIDER IMPLICATIONS OF THE FINDINGS: Rab11a-mediated trafficking of endometrial CAMs in EE cells can be explored further for its potential as a target for fertility regulation or infertility management. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the Indian Council of Medical Research (ICMR), the Department of Science and Technology (DST), the Council of Scientific and Industrial Research (CSIR), Government of India. No competing interests are declared.

Outcome of pregnancy with severe liver disease.

OBJECTIVES: To study the incidence, presentation, and outcome of patients with severe liver disease in an urban Indian population. METHOD: 26 patients with severe liver disease were identified in the study period of one year at a teaching tertiary care institute in Mumbai. Investigations included bedside Bleeding and Clotting Time (BT/CT), coagulation profiles and liver and renal function tests. Management was directed towards initial stabilization followed by early delivery in an intensive care setting. RESULT: 80.71% of the patients had HELLP (Hemolysis, Elevated Liver enzymes, Low Platelets) syndrome. The remaining were cases of acute fulminant hepatitis and acute fatty liver of pregnancy. The most consistent finding was thrombocytopenia (88.46%). Disseminated Intravascular Coagulopathy (DIC) was the most common complication (65%). BT/CT were 100% sensitive for the diagnosis of DIC. Maternal and perinatal mortality were 42.3% and 61.5% respectively. CONCLUSION: Intensive care facilities and an early diagnosis are essential for the management of mothers with severe liver disease. Prognosis is poor for patients with fulminant hepatitis and acute fatty liver. Screening for DIC is a must. Delay in recovery of biochemical parameters may indicate atypical disease. Patient education is essential at discharge.

Induction Of ovulation.

Sixty-one patients with anovulation as a cause of infertility were selected for our study. Various ovulation-inducing drugs were used like clomiphene citrate, human menopausal gonadotropin (hMG), human chorionic gonadotropin (hCG), bromergocryptine and leptadene. The response of the different drugs was observed by serial sonography for ovulation. Indeed there was a good response to clomiphene citrate, but those patients who failed to respond to clomiphene citrate and were frustrated with the use of hMG and hCG due to the cost and the complications of the therapy were put on Aloe compound and leptadene - an ayurvedic drug which enhances fertility in different ways.

Ligation of internal iliac arteries for control of pelvic haemorrhage.

This is a retrospective review of the internal iliac ligations (IAL) done over a period of 3 years. Both gynaecological and obstetric cases were considered. A total of 46 ligations were performed. The additional treatment required was hysterectomy to control haemorrhage. Intra-and post-operative complications were noted. A comparative review of the effectiveness of IAL in different situations is done and alternative modalities of treatment are considered.